Q13686 (ALKB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Alkylated DNA repair protein alkB homolog 1
EC=1.14.11.33

Alternative name(s):
Alpha-ketoglutarate-dependent dioxygenase ABH1
DNA lyase ABH1
EC=4.2.99.18
DNA oxidative demethylase ALKBH1

Gene names

Name:	ALKBH1
Synonyms:	ABH, ABH1, ALKBH

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	389 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Dioxygenase that repairs alkylated single-stranded DNA and RNA containing 3-methylcytosine by oxidative demethylation. Requires molecular oxygen, alpha-ketoglutarate and iron. May have a role in placental trophoblast lineage differentiation By similarity. Has DNA lyase activity and introduces double-stranded breaks at abasic sites. Cleaves both single-stranded DNA and double-stranded DNA at abasic sites, with the greatest activity towards double-stranded DNA with two abasic sites. DNA lyase activity does not require alpha-ketoglutarate and iron. Ref.5 Ref.6
Catalytic activity	The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate. DNA-base-CH3 + 2-oxoglutarate + O2 = DNA-base + formaldehyde + succinate + CO2.
Cofactor	Binds 1 Fe2+ ion per subunit. Ref.5
Subunit structure	Monomer. Interacts with DNAJB6 By similarity. Ref.6
Subcellular location	Mitochondrion. Nucleus By similarity. Note: Mainly localizes in euchromatin, largely excluded from heterochromatin and nucleoli By similarity. Ref.4 Ref.5
Tissue specificity	Ubiquitous. Ref.4 Ref.5
Sequence similarities	Belongs to the alkB family. Contains 1 Fe2OG dioxygenase domain.
Caution	Detected in cytoplasm and nucleus When expressed as fusion protein with an N-terminal tag, or when the first 26 N-terminal residues are removed (Ref.4 and Ref.5). The endogenous, unmodified protein localizes to mitochondria (Ref.5).
Sequence caution	The sequence CAA63047.1 differs from that shown. Reason: Frameshift at several positions.

Ontologies

Keywords
Biological process	DNA damage DNA repair RNA repair
Cellular component	Mitochondrion Nucleus
Coding sequence diversity	Polymorphism
Ligand	Iron Metal-binding
Molecular function	Dioxygenase Lyase Oxidoreductase
Technical term	Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	DNA dealkylation involved in DNA repair Inferred from direct assay Ref.5. Source: UniProtKB DNA demethylation Inferred from direct assay Ref.5. Source: UniProtKB RNA repair Inferred from direct assay Ref.5. Source: UniProtKB developmental growth Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from electronic annotation. Source: Compara negative regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara neuron migration Inferred from electronic annotation. Source: Compara neuron projection development Inferred from electronic annotation. Source: Compara oxidative demethylation Inferred from direct assay Ref.5. Source: UniProtKB placenta development Inferred from electronic annotation. Source: Compara
Cellular_component	mitochondrion Inferred from direct assay Ref.5. Source: UniProtKB nuclear euchromatin Inferred from electronic annotation. Source: Compara
Molecular_function	DNA-(apurinic or apyrimidinic site) lyase activity Inferred from direct assay Ref.6. Source: UniProtKB chemoattractant activity Inferred from electronic annotation. Source: Compara ferrous iron binding Inferred from direct assay Ref.5. Source: UniProtKB methylcytosine dioxygenase activity Inferred from direct assay Ref.5. Source: UniProtKB oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 389	389	Alkylated DNA repair protein alkB homolog 1		PRO_0000066668
Regions
	Domain	208 – 347	140	Fe2OG dioxygenase
	Region	177 – 179	3	Substrate binding By similarity
	Region	220 – 222	3	Alpha-ketoglutarate binding By similarity
	Region	338 – 344	7	Alpha-ketoglutarate binding By similarity
Sites
	Metal binding	231	1	Iron; catalytic By similarity
	Metal binding	233	1	Iron; catalytic By similarity
	Metal binding	287	1	Iron; catalytic By similarity
	Binding site	170	1	Substrate By similarity
	Binding site	261	1	Substrate By similarity
Natural variations
	Natural variant	135	1	M → I. Corresponds to variant rs17825440 [ dbSNP | Ensembl ].		VAR_048221
	Natural variant	324	1	M → L. Corresponds to variant rs6494 [ dbSNP | Ensembl ].		VAR_048222
Experimental info
	Mutagenesis	218	1	I → L: Reduces Fe2OG dioxygenase activity by 50%. Ref.5
	Mutagenesis	231	1	H → A: Near loss of Fe2OG dioxygenase activity. No effect on DNA lyase activity. Ref.5 Ref.6
	Mutagenesis	233	1	D → A: Loss of Fe2OG dioxygenase activity. No effect on DNA lyase activity. Ref.5 Ref.6
	Mutagenesis	287	1	H → A: Loss of Fe2OG dioxygenase activity. No effect on DNA lyase activity. Ref.5 Ref.6
	Mutagenesis	338	1	R → A: Reduced Fe2OG dioxygenase activity. Ref.5
	Mutagenesis	344	1	R → A: Reduced Fe2OG dioxygenase activity. Ref.5
	Sequence conflict	133	1	K → T in CAA63047. Ref.1
	Sequence conflict	266 – 267	2	TA → PP in CAA63047. Ref.1
	Sequence conflict	388	1	D → H in AAH25787. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q13686 [UniParc]. Last modified December 1, 2000. Version 2. Checksum: 539C4CE41D2D8AEC	FASTA	389	43,832
	10 20 30 40 50 60 MGKMAAAVGS VATLATEPGE DAFRKLFRFY RQSRPGTADL EGVIDFSAAH AARGKGPGAQ 70 80 90 100 110 120 KVIKSQLNVS SVSEQNAYRA GLQPVSKWQA YGLKGYPGFI FIPNPFLPGY QWHWVKQCLK 130 140 150 160 170 180 LYSQKPNVCN LDKHMSKEET QDLWEQSKEF LRYKEATKRR PRSLLEKLRW VTVGYHYNWD 190 200 210 220 230 240 SKKYSADHYT PFPSDLGFLS EQVAAACGFE DFRAEAGILN YYRLDSTLGI HVDRSELDHS 250 260 270 280 290 300 KPLLSFSFGQ SAIFLLGGLQ RDEAPTAMFM HSGDIMIMSG FSRLLNHAVP RVLPNPEGEG 310 320 330 340 350 360 LPHCLEAPLP AVLPRDSMVE PCSMEDWQVC ASYLKTARVN MTVRQVLATD QNFPLEPIED 370 380 EKRDISTEGF CHLDDQNSEV KRARINPDS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and functional analysis of a human cDNA encoding an Escherichia coli AlkB homolog, a protein involved in DNA alkylation damage repair." Wei Y.F., Carter K.C., Wang R.P., Shell B.K. Nucleic Acids Res. 24:931-937(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Synovial sarcoma.
[2]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas.
[4]	"Expression and sub-cellular localization of human ABH family molecules." Tsujikawa K., Koike K., Kitae K., Shinkawa A., Arima H., Suzuki T., Tsuchiya M., Makino Y., Furukawa T., Konishi N., Yamamoto H. J. Cell. Mol. Med. 11:1105-1116(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[5]	"Human AlkB homolog 1 is a mitochondrial protein that demethylates 3-methylcytosine in DNA and RNA." Westbye M.P., Feyzi E., Aas P.A., Vagbo C.B., Talstad V.A., Kavli B., Hagen L., Sundheim O., Akbari M., Liabakk N.B., Slupphaug G., Otterlei M., Krokan H.E. J. Biol. Chem. 283:25046-25056(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, COFACTOR, SUBCELLULAR LOCATION, MUTAGENESIS OF ILE-218; HIS-231; ASP-233; HIS-287; ARG-338 AND ARG-344, MASS SPECTROMETRY, TISSUE SPECIFICITY.
[6]	"Human AlkB homologue 1 (ABH1) exhibits DNA lyase activity at abasic sites." Muller T.A., Meek K., Hausinger R.P. DNA Repair 9:58-65(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF HIS-231; ASP-233 AND HIS-287, SUBUNIT.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X91992 mRNA. Translation: CAA63047.1. Frameshift. AC008044 Genomic DNA. Translation: AAF01478.1. BC025787 mRNA. Translation: AAH25787.1.
IPI	IPI00014482.
PIR	S64736.
RefSeq	NP_006011.2. NM_006020.2.
UniGene	Hs.94542.
3D structure databases
ProteinModelPortal	Q13686.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000216489.
PTM databases
PhosphoSite	Q13686.
Polymorphism databases
DMDM	12643239.
Proteomic databases
PaxDb	Q13686.
PRIDE	Q13686.
Protocols and materials databases
DNASU	8846.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000216489; ENSP00000216489; ENSG00000100601.
GeneID	8846.
KEGG	hsa:8846.
UCSC	uc001xuc.1. human.
Organism-specific databases
CTD	8846.
GeneCards	GC14M078138.
H-InvDB	HIX0011855.
HGNC	HGNC:17911. ALKBH1.
HPA	HPA044087.
MIM	605345. gene.
neXtProt	NX_Q13686.
PharmGKB	PA134906996.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG3145.
HOGENOM	HOG000033905.
HOVERGEN	HBG050487.
InParanoid	Q13686.
KO	K10765.
OMA	KKYSADH.
OrthoDB	EOG4868CJ.
PhylomeDB	Q13686.
Gene expression databases
ArrayExpress	Q13686.
Bgee	Q13686.
CleanEx	HS_ALKBH1.
Genevestigator	Q13686.
GermOnline	ENSG00000100601. Homo sapiens.
Family and domain databases
InterPro	IPR004574. Alkb. IPR005123. Oxoglu/Fe-dep_dioxygenase. [Graphical view]
Pfam	PF13532. 2OG-FeII_Oxy_2. 1 hit. [Graphical view]
TIGRFAMs	TIGR00568. alkb. 1 hit.
PROSITE	PS51471. FE2OG_OXY. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	8846.
NextBio	33208.
SOURCE	Search...

Entry information

Entry name

ALKB1_HUMAN

Accession

Primary (citable) accession number: Q13686
Secondary accession number(s): Q8TAU1, Q9ULA7

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	December 1, 2000
Last modified:	April 3, 2013
This is version 105 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.